Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1731 | 5416;5417;5418 | chr2:178776673;178776672;178776671 | chr2:179641400;179641399;179641398 |
| N2AB | 1731 | 5416;5417;5418 | chr2:178776673;178776672;178776671 | chr2:179641400;179641399;179641398 |
| N2A | 1731 | 5416;5417;5418 | chr2:178776673;178776672;178776671 | chr2:179641400;179641399;179641398 |
| N2B | 1685 | 5278;5279;5280 | chr2:178776673;178776672;178776671 | chr2:179641400;179641399;179641398 |
| Novex-1 | 1685 | 5278;5279;5280 | chr2:178776673;178776672;178776671 | chr2:179641400;179641399;179641398 |
| Novex-2 | 1685 | 5278;5279;5280 | chr2:178776673;178776672;178776671 | chr2:179641400;179641399;179641398 |
| Novex-3 | 1731 | 5416;5417;5418 | chr2:178776673;178776672;178776671 | chr2:179641400;179641399;179641398 |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs876658072  |
-0.344 | 1.0 | D | 0.695 | 0.746 | 0.458917189328 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| D/G | rs876658072 |
-0.344 | 1.0 | D | 0.695 | 0.746 | 0.458917189328 | gnomAD-4.0.0 | 4.7719E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.56942E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9826 | likely_pathogenic | 0.9854 | pathogenic | -0.392 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.621577839 | None | None | I |
| D/C | 0.9959 | likely_pathogenic | 0.9963 | pathogenic | -0.036 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| D/E | 0.9667 | likely_pathogenic | 0.9634 | pathogenic | -0.521 | Destabilizing | 1.0 | D | 0.441 | neutral | D | 0.55110083 | None | None | I |
| D/F | 0.9961 | likely_pathogenic | 0.9962 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | I |
| D/G | 0.9956 | likely_pathogenic | 0.9967 | pathogenic | -0.645 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | D | 0.762878097 | None | None | I |
| D/H | 0.9861 | likely_pathogenic | 0.9861 | pathogenic | -0.541 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | D | 0.609857742 | None | None | I |
| D/I | 0.9945 | likely_pathogenic | 0.9949 | pathogenic | 0.242 | Stabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| D/K | 0.9976 | likely_pathogenic | 0.9975 | pathogenic | -0.164 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| D/L | 0.9865 | likely_pathogenic | 0.9876 | pathogenic | 0.242 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| D/M | 0.9985 | likely_pathogenic | 0.9986 | pathogenic | 0.545 | Stabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| D/N | 0.9134 | likely_pathogenic | 0.9309 | pathogenic | -0.358 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | D | 0.576091418 | None | None | I |
| D/P | 0.998 | likely_pathogenic | 0.9983 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| D/Q | 0.997 | likely_pathogenic | 0.9968 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| D/R | 0.9974 | likely_pathogenic | 0.9974 | pathogenic | -0.038 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| D/S | 0.9623 | likely_pathogenic | 0.9664 | pathogenic | -0.522 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/T | 0.9953 | likely_pathogenic | 0.9957 | pathogenic | -0.336 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| D/V | 0.9872 | likely_pathogenic | 0.9889 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.786 | deleterious | D | 0.573521472 | None | None | I |
| D/W | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| D/Y | 0.9709 | likely_pathogenic | 0.9702 | pathogenic | -0.151 | Destabilizing | 1.0 | D | 0.759 | deleterious | D | 0.591241371 | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.